HRP930558A2 - Process for the preparation of norfloxacine intermediates - Google Patents
Process for the preparation of norfloxacine intermediates Download PDFInfo
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- HRP930558A2 HRP930558A2 HR930558A HRP930558A HRP930558A2 HR P930558 A2 HRP930558 A2 HR P930558A2 HR 930558 A HR930558 A HR 930558A HR P930558 A HRP930558 A HR P930558A HR P930558 A2 HRP930558 A2 HR P930558A2
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- Prior art keywords
- carbon atoms
- general formula
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- group containing
- halogen
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Links
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 239000000543 intermediate Substances 0.000 title description 3
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 title description 2
- 229960001180 norfloxacin Drugs 0.000 title description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 5
- 150000001638 boron Chemical class 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 4
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 3
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 description 13
- -1 ethyl-1-ethyl-6-fluoro-chloro-4-oxo-1,4-dihydro-quinoline-3-carboxylate Chemical compound 0.000 description 7
- WNNSMMJBBOPPOT-UHFFFAOYSA-N 7-chloro-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(Cl)C=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 WNNSMMJBBOPPOT-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 5
- 239000004327 boric acid Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- NGBZZCXZVDYZQK-UHFFFAOYSA-N ethyl 7-chloro-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound ClC1=C(F)C=C2C(=O)C(C(=O)OCC)=CN(CC)C2=C1 NGBZZCXZVDYZQK-UHFFFAOYSA-N 0.000 description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical class NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/04—Esters of boric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Peptides Or Proteins (AREA)
- Saccharide Compounds (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thin Film Transistor (AREA)
- Cephalosporin Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
Područje tehnike
Izum je iz područja organske kemije i odnosi se na intermedijere norfloksacina.
Tehnički problem
Ovaj izum se odnosi na nove intermedijere primjenljive u dobivanju norfloksacina. Točnije, izum se odnosi na nove anhidride 1-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilne kiseline i bornih kiselina/ i postupak za njihovo pripremanje.
Stanje tehnike
Poznato je da etil-l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolm-3-karboksilat (Journal of Medicinal Chemistry 23, 1358 (1980); Japanska parentna specifikacija br. 80 33.453) je primjenljiv intermedijer za dobivanje l-etil-6-fluoro-7-supstituiranih-4-okso-l,4-dihidro-kinolm-3-karboksilnih kiselina, koje imaju antibakterijski efekt (Ann. Microbiol. /Pariz/ 1981, 123 A, 267; Journal of Medicinal Chemistry 1980, 23, 1358; Pathol. Biol. 1982 30, 394; Cyo Yakuri, 1983, 25, 475; PathoL Biol. 1983, 31, 501; Antimicrob. Agents Chemother. 1980, 17, 103; 1981, 19, 188; 1981, 20, 265; C R. Scances Acad. Sci. Ser. 3, 1981, 292, 37).
Posljednji spojevi mogu biti dobiveni u dva stupnja reakcije etil-l-etil-6-fluoro-klor-4-okso-l,4-dihidro-kinolin-3-karboksilata sa cikličnim aminom na temperaturi iznad 100°C u prisutnosti otapala tijekom više sati i podvrgavanjem etil-l-etil-fluoro-7-supstituiranog-4-okso-l,4-dihidro-kinolm-3-karboksilata, tako dobivenog, hidrolizi; radi poboljšanja spomenuta dva stupnja mogu biti izmijenjena, ako se želi (Japanske patentne specifikacije br. 863.429:
870.917; 879.106 i 890.223; DOS br. 2.840.910 i Francuskoj patentnoj prijavi br. 2.424.919).
Gornji postupci su praćeni s više nedostataka. Reakcijsko vrijeme je predugo. Međutim, reakcija izmjene halogen/amino grupa, nije selektivna i dodatno željenoj klor/amin reakciji u položaju 7, u znatnoj mjeri, se odvija također i fluor/amin izmjena u položaju 6.
Pronađeno je da se selektivnost željene reakcije izmjene halogen/amm u položaju 7 može uvećati reakcijom cikličnog amina s anhidridom opće formule 1 (gdje R i Rl označavaju alifatsku aciloksi grupu, koja obuhvaća 2-5 atoma ugljika i po izboru supstituiranom s halogenom ili aromatičnu aciloksi grupu koja, obuhvaća 7-11 atoma ugljika). Daljnja prednost ovog postupka je znatno kraće reakcijsko vrijeme.
Opis rješenja tehničkog problema s primjerima izvođenja
Prema ovom izumu osiguran je postupak za dobijanje spojeva opće formule I:
[image]
(gdje R i Rl označavaju alifatsku aciloksi grupu, koja obuhvaća 2-5 atoma ugljika i po izboru supstituiranu s halogenom ili aromatičnu aciloksi grupu. koja sadrži 7-11 atoma ugljika), koja obuhvaća reakciju spoja opće formule 11:
[image]
(gdje R2 označava vodik ili alkil koji sadrži 1-4 atoma ugljika) sa derivatom bora opće formule III:
[image]
(gdje R3 R4 i R5 označavaju alkil grupu, koja obuhvaća 1-4 atoma ugljika i po izboru je supstituirana s halogenom ili aril grupu, koja sadrži 6-10 atoma ugljika).
Reakcija kinolin-3-karboksilne kiseline opće formule II i derivata bora općc formule III, može se povoljno izvoditi u, po izboru, halogeniranoj organskoj karboksilnoj kiselini, koja također može sadržavati odgovarajući anhidrid kiseline, na temperaturi između 0 i 200°C. Spoj opće formule I, tako izgrađen, taloži se iz reakcijske smjese spontano ili hlađenjem, te se može odvojiti npr. filtriranjem.
Reakcija se, međutim, može izvesti u drugim otapalima (npr. sulfoksid, amidi. piridin, aromatični ugljikovodici), ako se želi.
Derivati bora opće formule III, mogu biti korišteni u molarnom odnosu 1-5 mola u odnosu na 1 mol kinolin-3-karboksilne kiseline derivata opće formule II.
Ostali detalji ovog izuma nalaze se u slijedećim primjerima bez ograničavanja obima zaštite u primjerima.
Primjer 1
Mješavina od 9,3 g borne kiseline i 70 g propion anhidrida se miješa na 100°C tijekom 15 minuta, nakon čega se reakcijska smjesa grije do točke vrenja. Nakon pola sata temperatura se snizi do 110°C i dodaje se 29,8 g etil-l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilata. Reakcijska smjesa, koja prelazi u suspenziju za nekoliko minuta se miješa na 110°C tijekom 2 sata, ohlađena je do sobne temperature i razblažena sa 300 ml vode.
Reakcijska smjesa se ohladi i nataloženi kristali se profiltriraju. Tako je dobiveno 41,5 g l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilne kiselme-bor-di(propioniloksi)-anhidrida, prinos 97,7%. Proizvod se razlaže na
252°C.
Analiza za C18H18BFClNO7
Izračunano: C = 50,79%, H = 4,26%, N = 4,29%;
Nađeno: C = 50,94%, H = 4,15%, N = 3,41%.
Primjer 2
Mješavina od 46,3 g borne kiseline i 345 g propion anhidrida je miješana na 100°C tijekom 15 minuta, nakon čega je reakcijska smjesa zagrijana do točke vrenja. Nakon pola sata reakcijska temperatura je snižena do 110°C i dodano je 134,5 g l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilne kiseline. Reakcijska smjesa je miješana na 110°C 2 sata i ohlađena ispod 10°C Reakcijska smjesa je razblažena sa 150 ml vode i ostavljena da kristalizira u hladnjaku preko noći. Slijedećeg jutra nataloženi kristali su profiltrirani. isprani s vodom i osušeni na vakuumu. Tako je dobiveno 208,6 g l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolm-3-karboksilnekiselme-bor-di(propioniloksi)-anhidrida, prinos 98%. Proizvod se topi na 269°C (razlaže se). Smjesa izgrađenog proizvoda sa nekom količinom spoja dobivenog prema Primjeru 1. pokazuje sniženu točku topljenja.
Primjer 3
Mješavina od 9,3 g borne kiseline i 54,1 g aceta anhidrida je grijana na 100°C 30 minuta. Reakcijska smjesa je ohlađena do 80°C i dodano je 29,8 g etil-l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilata. Reakcijska smjesa je miješana na 110°C 2 sata, ohlađena je ispod 10°C i razblažena sa 100 ml vode. Ohlađena reakcijska smjesa je ostavljena da kristalizira u hladnjaku preko noći. Slijedećeg jutra nataloženi kristali su profiltrirani. isprani s vodom i osušeni. Tako je dobiveno 33,5 g l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolinm-3-karboksilne kiseline-bor-di(acetoksi)-anhidrid. Prinos 84,4%. Proizvod se razlaže na 274°C.
Analiza za C16H14FClBNO7
Izračunano: C = 48,34%, H = 3,54%, N = 3,52%;
Nađeno: C = 48,48%, H = 3,43%, N = 3,57%.
Naputak o najboljem, podnositelju prijave poznatom načinu gospodarske upotrebe izuma
Predmetni izum se može najbolje primijeniti u gospodarstvu ako se ostvaruje na slijedeći način:
Mješavina od 9,3 g borne kiseline i 70 g propion anhidrida se miješa na 100°C tijekom 15 minuta, nakon čega se reakcijska smjesa grije do točke vrenja. Nakon pola sata temperatura se snizi do 110°C i dodaje se 29,8 g etil-l-etil-6-fluoro-7-klor-4-okso-l,4-dihidro-kinolin-3-karboksilata. Reakcijska smjesa, koja prelazi u suspenziju za nekoliko minuta, miješa se na 110°C tijekom 2 sata, ohlađena je do sobne temperature i razblažena sa 300 ml vode.
Reakcijska smjesa se ohladi i nataloženi kristali se profiltriraju. Tako je dobiveno 41,5 g 1-etil-6-fluoro-7-klor-4-okso- 1,4-dihidro-kinolin-3-karboksilne kiseline-bor-di(propioniloksi)-anhidrida, prinos 97,7%. Proizvod se razlaže na
252°C,
Analiza za C18H18BFClNO7
Izračunano: C = 50,79%, H = 4,26%, N = 4,29%;
Nađeno: C = 50,94%, H = 4,15%, N = 3,41%.
Claims (6)
1. Spoj opće formule I:
[image]
naznačen time, što R i R1 označavaju alifatsku aciloksi grupu koja sadrži 2-5 atoma ugljika i po izboru supstituiranu halogenom ili aromatičnu aciloksi grupu koja sadrži 7-11 atoma ugljika.
2. Postupak za dobivanje spojeva opće formule I:
[image]
(gdje R i R1 označavaju alifatsku aciloksi grupu koja sadrži 2-5 atoma ugljika i po izboru supstituiranu halogenom ili aromatičnu aciloksi grupu koja sadrži 7-11 atoma ugljika), naznačen time, što obuhvaća reakciju spoja opće formule II:
[image]
(gdje R2 označava vodik ili alkil grupu koja sadrži 1-4 atoma ugljika) s derivatom bora opće formule III:
[image]
(gdje R3 R4 i R5 označavaju alkil grupu koja sadrži 1-4 atoma ugljika i po izboru supstituiranu halogenom ili aril grupu koja sadrži 6-10 atoma ugljika).
3. Postupak prema zahtjevu 2, naznačen time, što obuhvaća vršenje reakcije spojeva općih formula II i III u prisutnosti otapala.
4. Postupak prema zahtjevu 2, naznačen time, što se reakcija spojeva općih formula II i III izvodi na temperaturi izmeđdu 0 i 150°C
5. Spojevi opće formule I, naznačen time, što su dobiveni nekim od postupaka prema zahtjevima 2-4.
6. Postupak, naznačen time, kao što je opisan prije sa posebnim osvrtom na Primjere.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU854693A HU196218B (en) | 1985-12-09 | 1985-12-09 | Process for preparing quinoline carboxylic acid boric acid anhydrides |
| YU2108/86A YU45388B (en) | 1985-12-09 | 1986-12-09 | Process for obtaining norfloxacine intermediary |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP930558A2 true HRP930558A2 (en) | 1996-04-30 |
Family
ID=10968688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR930558A HRP930558A2 (en) | 1985-12-09 | 1993-03-26 | Process for the preparation of norfloxacine intermediates |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4803274A (hr) |
| EP (1) | EP0250535B1 (hr) |
| JP (1) | JPH0742299B2 (hr) |
| KR (1) | KR940009028B1 (hr) |
| AT (1) | ATE53212T1 (hr) |
| CA (1) | CA1284800C (hr) |
| CS (1) | CS265228B2 (hr) |
| DD (1) | DD252608A5 (hr) |
| DE (1) | DE3671628D1 (hr) |
| DK (1) | DK412587A (hr) |
| FI (1) | FI84072C (hr) |
| HR (1) | HRP930558A2 (hr) |
| HU (1) | HU196218B (hr) |
| NO (1) | NO169076C (hr) |
| SI (1) | SI8612108A8 (hr) |
| SU (1) | SU1604156A3 (hr) |
| WO (1) | WO1987003595A1 (hr) |
| YU (1) | YU45388B (hr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI8810667A8 (en) * | 1987-04-08 | 1996-04-30 | Chinoin Gyogyszer Es Vegyeszet | Anhydride of quinoline carboxylic acid of boron acid and process for their production. |
| HU198709B (en) * | 1987-04-08 | 1989-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing quinoline-carboxylic acid derivatives |
| US5380845A (en) * | 1987-06-24 | 1995-01-10 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. | Process for the preparation of quinoline carboxylic acid derivatives |
| GR910100517A (el) * | 1991-12-30 | 1993-08-31 | Kyorin Seiyaku Kk | Δις(ακυλοξυ-ο) βορικος εστερας του (6,7-υποκατεστημενου-8-αλκοξυ-1- κυκλοπροπυλ-1,4,-διυδρο-4-οξο-3-κινολινοκαρβοξυλικου οξεως-ο3,ο4)και αλας αυτου, και μεθοδος παρασκευης αυτου. |
| ES2077490B1 (es) * | 1992-11-18 | 1996-10-16 | Marga Investigacion | Esteres trimetilsililicos y solvatos de quelatos de acidos quinolin-3-carboxilicos. preparacion y aplicacion al proceso de quinolonas. |
| ES2092963B1 (es) * | 1995-04-12 | 1997-12-16 | Sint Quimica Sa | Procedimiento para la preparacion del acido 1-ciclopropil-6-fluoro-1, 4-dihidro-7-(1s,4s)-5-metil-2,5-diazabiciclo(2.2.1) hept-2-il)-4-oxo-3-quinolincarboxilico y sus sales. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1195749A (en) * | 1966-12-19 | 1970-06-24 | Lubrizol Corp | Sulfur-Containing Cycloaliphatic Reaction Products and their use in Lubricant Compositions |
| JPS53141286A (en) | 1977-05-16 | 1978-12-08 | Kyorin Seiyaku Kk | Novel substituted quinolinecarboxylic acid |
| SE444566B (sv) | 1977-09-20 | 1986-04-21 | Bellon Labor Sa Roger | 7-dialkylamin-6-halogen-4-oxo-1,4-dihydrokinolin-3-karboxylsyra, forfarande for framstellning derav och farmaceutiskt preparat derav |
| JPS6011913B2 (ja) * | 1977-12-27 | 1985-03-28 | 広栄化学工業株式会社 | １，８−ナフチリジン誘導体ならびにその製造方法 |
| JPS54138582A (en) | 1978-04-19 | 1979-10-27 | Kyorin Seiyaku Kk | Substituted quinolinecarboxylic acid |
| FR2424919B1 (fr) | 1978-05-03 | 1980-10-31 | Kyorin Seiyaku Kk | Acide quinoleinecarboxylique substitue et ses derives et leur utilisation comme agents antibacteriens |
| JPS5533453A (en) | 1978-08-31 | 1980-03-08 | Dainippon Pharmaceut Co Ltd | Preventive and remedy for infectious disease of fish |
| JPS5845426B2 (ja) | 1978-09-29 | 1983-10-08 | 杏林製薬株式会社 | 置換キノリンカルボン酸誘導体 |
| JPS5762259A (en) | 1980-09-05 | 1982-04-15 | Kyorin Pharmaceut Co Ltd | Preparation of substituted quinolinecarboxylic acid derivative |
| JPS59122470A (ja) | 1982-12-27 | 1984-07-14 | Dai Ichi Seiyaku Co Ltd | キノリン−３−カルボン酸誘導体の製造法 |
| JPH0833453B2 (ja) | 1987-05-30 | 1996-03-29 | 大阪瓦斯株式会社 | 金属管の接触位置の検出方法 |
-
1985
- 1985-12-09 HU HU854693A patent/HU196218B/hu not_active IP Right Cessation
-
1986
- 1986-12-08 CA CA000524725A patent/CA1284800C/en not_active Expired - Lifetime
- 1986-12-09 SI SI8612108A patent/SI8612108A8/sl unknown
- 1986-12-09 YU YU2108/86A patent/YU45388B/xx unknown
- 1986-12-09 US US07/105,298 patent/US4803274A/en not_active Expired - Fee Related
- 1986-12-09 EP EP87900246A patent/EP0250535B1/en not_active Expired - Lifetime
- 1986-12-09 KR KR1019870700687A patent/KR940009028B1/ko not_active IP Right Cessation
- 1986-12-09 JP JP62500207A patent/JPH0742299B2/ja not_active Expired - Lifetime
- 1986-12-09 CS CS869089A patent/CS265228B2/cs unknown
- 1986-12-09 WO PCT/HU1986/000068 patent/WO1987003595A1/en active IP Right Grant
- 1986-12-09 DD DD86297301A patent/DD252608A5/de not_active IP Right Cessation
- 1986-12-09 DE DE8787900246T patent/DE3671628D1/de not_active Expired - Fee Related
- 1986-12-09 AT AT87900246T patent/ATE53212T1/de not_active IP Right Cessation
-
1987
- 1987-08-03 NO NO873247A patent/NO169076C/no unknown
- 1987-08-07 DK DK412587A patent/DK412587A/da not_active Application Discontinuation
- 1987-08-07 FI FI873443A patent/FI84072C/fi not_active IP Right Cessation
- 1987-08-07 SU SU874203191A patent/SU1604156A3/ru active
-
1993
- 1993-03-26 HR HR930558A patent/HRP930558A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FI873443A0 (fi) | 1987-08-07 |
| NO169076C (no) | 1992-05-06 |
| NO873247D0 (no) | 1987-08-03 |
| EP0250535B1 (en) | 1990-05-30 |
| FI873443A (fi) | 1987-08-07 |
| NO873247L (no) | 1987-08-03 |
| EP0250535A1 (en) | 1988-01-07 |
| US4803274A (en) | 1989-02-07 |
| FI84072C (fi) | 1991-10-10 |
| CS908986A2 (en) | 1988-03-15 |
| CA1284800C (en) | 1991-06-11 |
| DK412587D0 (da) | 1987-08-07 |
| JPS63501955A (ja) | 1988-08-04 |
| KR880700803A (ko) | 1988-04-12 |
| SU1604156A3 (ru) | 1990-10-30 |
| JPH0742299B2 (ja) | 1995-05-10 |
| CS265228B2 (en) | 1989-10-13 |
| YU45388B (en) | 1992-05-28 |
| KR940009028B1 (ko) | 1994-09-29 |
| HU196218B (en) | 1988-10-28 |
| SI8612108A8 (en) | 1996-10-31 |
| YU210886A (en) | 1987-12-31 |
| ATE53212T1 (de) | 1990-06-15 |
| DK412587A (da) | 1987-08-07 |
| NO169076B (no) | 1992-01-27 |
| HUT44566A (en) | 1988-03-28 |
| DE3671628D1 (de) | 1990-07-05 |
| DD252608A5 (de) | 1987-12-23 |
| WO1987003595A1 (en) | 1987-06-18 |
| FI84072B (fi) | 1991-06-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| ODBC | Application rejected |